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  • Review Article
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Anti-MDA5 antibody-positive dermatomyositis: pathogenesis and clinical progress

Nature Reviews Rheumatology volume 20, pages 48–62 (2024)Cite this article

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Abstract

Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a subtype of dermatomyositis. Although the aetiology and pathology remain unclear, increasing evidence suggests that viral infection is a potential trigger of MDA5-DM. Multiple factors, including T cells, B cells, neutrophils and macrophages, are implicated in the pathophysiology of MDA5-DM. Distinctive skin rashes, rapidly progressive interstitial lung disease, peripheral lymphopenia and elevated serum ferritin levels are the most prominent clinical and laboratory features of MDA5-DM. Concomitant infection is a common complication of MDA5-DM. The proper evaluation of patients with MDA5-DM requires knowledge of the disease heterogeneity and clinical course variability. Several biomarkers, including serum levels of anti-MDA5 antibodies and biomarkers related to macrophage activation, have been identified as useful tools for monitoring disease activity and prognosis. MDA5-DM shows a poor response to conventional glucocorticoid and immunosuppressant therapy and has a poor overall prognosis. Therefore, there is an urgent need to explore the key pathogenic mechanisms of MDA5-DM and develop novel therapeutic options for patients. This Review discusses recent clinical progress and pathogenic findings of MDA5-DM.

Key points

  • Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a subtype of dermatomyositis with a poor prognosis that typically presents as skin manifestations and rapidly progressive interstitial lung disease.

  • Although the aetiology of MDA5-DM is unknown, emerging epidemiological evidence of the seasonal and geographical distributions of MDA5-DM implicate viral infection as a potential trigger.

  • The pathomechanism of MDA5-DM is complex, with a potential contributing role for T cells, B cells, neutrophils, macrophages and natural killer cells.

  • Proper evaluation of patients with MDA5-DM requires knowledge of the diversity in clinical features, with several studies showing that MDA5-DM can be grouped into different clinical subtypes.

  • Various biomarkers that predict disease activity and severity have been identified and used in clinical practice, including anti-MDA5 antibodies, ferritin and KL-6.

  • Given the absence of randomized controlled trials in MDA5-DM, current therapeutic approaches rely on empirical evidence; therefore, novel treatments are needed to improve the prognosis of patients with MDA5-DM.

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Fig. 1: Mucocutaneous features of MDA5-DM.
Fig. 2: Lung manifestations of MDA5-DM.
Fig. 3: Implicated processes in the immunopathogenesis of MDA5-DM.

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Acknowledgements

The work of G.W. is partially supported by National High Level Hospital Clinical Research Funding (grant number 2022-NHLHCRF-YS-02). The work of X.L. is partially supported by the Natural Science Foundation of Beijing Municipality (grant number 7232145). The work of Q.P. is partially supported by the National Natural Science Foundation of China (grant number 82171788).

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  1. Department of Rheumatology, Key Myositis Laboratories, China-Japan Friendship Hospital, Beijing, China

    Xin Lu, Qinglin Peng & Guochun Wang

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Lu, X., Peng, Q. & Wang, G. Anti-MDA5 antibody-positive dermatomyositis: pathogenesis and clinical progress. Nat Rev Rheumatol 20, 48–62 (2024). https://doi.org/10.1038/s41584-023-01054-9

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